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PORTEC-4a: Molecular Profile-based Versus Standard Adjuvant Radiotherapy in Endometrial Cancer (PORTEC-4a)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03469674
Recruitment Status : Recruiting
First Posted : March 19, 2018
Last Update Posted : August 18, 2021
Sponsor:
Collaborators:
Dutch Cancer Society
Comprehensive Cancer Centre The Netherlands
Information provided by (Responsible Party):
Carien Creutzberg, Leiden University Medical Center

Study Description
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Brief Summary:
This is prospective, multicenter, randomised phase III trial among women with endometrial cancer with high-intermediate risk features to investigate the role of an integrated clinicopathological and molecular risk profile to determine if participants should receive no adjuvant therapy, vaginal brachytherapy or external beam radiotherapy based on a favourable, intermediate or unfavourable profile as compared to standard adjuvant vaginal brachytherapy.

Condition or disease Intervention/treatment Phase
Endometrial Cancer Stage I Endometrial Cancer Stage II Radiation: Vaginal brachytherapy Radiation: External beam radiotherapy Other: Observation Phase 3

Detailed Description:
Adjuvant therapy for women with endometrial cancer has increasingly been tailored to prognostic factors to prevent overtreatment and select those women for adjuvant treatment who will have a clinically relevant reduction of the risk of relapse by the adjuvant treatment. Risk profiles have traditionally been based on clinicopathological factors such as age, stage, grade, LVSI and depth of invasion. Newer, both molecular-genetic (the cancer genome atlas subgroups) or immunohistochemistry-based (L1-CAM) risk factors have become available which are strongly related to outcomes and risk of cancer spread. In a comprehensive analysis of the PORTEC-1 and-2 biobank an integrated clinicopathological and molecular risk profile was determined which separated the current high-intermediate risk group of endometrial cancer in 3 separate groups (favourable, intermediate or unfavourable) with clearly separated outcomes, which is now prospectively tested in the clinic to determine adjuvant treatment. This is the first randomised trial using the molecular risk factors to assign adjuvant treatment for women with stage I-II high-intermediate risk endometrial cancer.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 550 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 2:1 randomisation to adjuvant treatment assignment based on the integrated molecular risk profile or standard adjuvant vaginal brachytherapy
Masking: None (Open Label)
Masking Description: Evaluation of outcomes is done without information on randomised arm
Primary Purpose: Treatment
Official Title: Randomised Phase III Trial of Molecular Profile-based Versus Standard Recommendations for Adjuvant Radiotherapy for Women With Early Stage Endometrial Cancer: PORTEC-4a Trial
Actual Study Start Date : June 10, 2016
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2028
Arms and Interventions
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Arm Intervention/treatment
Experimental: Molecular profile based treatment
Determination of the integrated clinicopathological and molecular profile to determine adjuvant treatment: observation for favourable profile; vaginal brachytherapy for intermediate profile; external beam radiotherapy for unfavourable profile
 Radiation: Vaginal brachytherapy
Internal radiation of the vaginal vault using a vaginal cylinder, 21 Gy in 3 out-patient sessions over 2 weeks

Radiation: External beam radiotherapy
External beam pelvic radiotherapy on a linear accelerator, 48.6 Gy in 27 out-patients sessions over 5.5 weeks

Other: Observation
No radiation therapy, but active follow-up and quality of life questionnaires as in the groups who have adjuvant treatment
Active Comparator: Vaginal brachytherapy
Adjuvant vaginal brachytherapy (standard treatment)
 Radiation: Vaginal brachytherapy
Internal radiation of the vaginal vault using a vaginal cylinder, 21 Gy in 3 out-patient sessions over 2 weeks


Outcome Measures
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Primary Outcome Measures :
  1. Vaginal recurrence [ Time Frame: 5 years ]
    Total vaginal recurrence and vaginal recurrence as first failure


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 5 years ]
    Treatment-related symptoms according to CTCAE v 4.0

  2. Health-related cancer-specific quality of life [ Time Frame: 5 years ]
    Cancer-specific quality of life (European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQC-30) - clinically relevant changes on QLQC30 functioning scales, general quality of life and general cancer symptoms

  3. Endometrial cancer-related symptoms and quality of life [ Time Frame: 5 years ]
    Endometrial cancer-related specific symptoms (EORTC EN24 module)- clinically relevant changes on these scales (quite a bit/very much vs no or mild symptoms)

  4. Relapse-free survival [ Time Frame: 5 years ]
    Relapse-free survival (survival without relapse)

  5. Survival [ Time Frame: 5 years ]
    Overall survival (all-cause death)

  6. 5-year vaginal control including treatment for relapse [ Time Frame: 5 years ]
    Long-term local control including salvage treatment for local relapse

  7. Pelvic recurrence (total) [ Time Frame: 5 years ]
    Total pelvic recurrences

  8. Pelvic recurrence as first failure [ Time Frame: 5 years ]
    Pelvic recurrence as first failure

  9. Distant recurrence (total) [ Time Frame: 5 years ]
    Total distant recurrences

  10. Distant recurrence as first failure [ Time Frame: 5 years ]
    Distant recurrence as first failure

  11. Endometrial cancer related health care costs [ Time Frame: 5 years ]
    All hospital based health care costs used with primary treatment or during followup for treatment of adverse events and/or treatment for relapse


Other Outcome Measures:
  1. Recurrence (vaginal and total) per risk profile [ Time Frame: 5 years ]
    Vaginal, pelvic and distant relapse split by risk profile and compared between the 2 arms


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed endometrioid type endometrial carcinoma, International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I, with one of the following combinations of stage, grade, age, and lymph-vascular space invasion (LVSI):

    1. Stage IA, grade 3 (any age, with or without LVSI)
    2. Stage IB, grade 1 or 2 and age >60 years
    3. Stage IB, grade 1-2 with documented LVSI
    4. Stage IB, grade 3 without LVSI
    5. Stage II (microscopic), grade 1
  • World Health Organization (WHO)-performance status 0-2
  • Written informed consent

Exclusion Criteria:

  • Any other stage and type of endometrial carcinoma
  • Histological types serous carcinoma or clear cell carcinoma (at least 10% if mixed type), or undifferentiated or neuroendocrine carcinoma
  • Uterine sarcoma (including carcinosarcoma)
  • Previous malignancy (except for non-melanomatous skin cancer) < 5 yrs
  • Previous pelvic radiotherapy
  • Expected interval between the operation and start of radiotherapy exceeding 8 weeks
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03469674


Contacts
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Contact: Chief Investigator +3165263057 c.l.creutzberg@lumc.nl
Contact: Karen Verhoeven-Adema, PhD +3188 234 6125 portec@iknl.nl

Locations
Show Show 31 study locations
Sponsors and Collaborators
Leiden University Medical Center
Dutch Cancer Society
Comprehensive Cancer Centre The Netherlands
Investigators
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Study Chair: Carien L. Creutzberg, MD, PhD Leiden University Medical Center, Dept of Radiation Oncology
Principal Investigator: Remi A. Nout, MD, PhD ErasmusMC Dept of Radiation Oncology
Principal Investigator: Anne-Sophie van den Heerik, MD Leiden University Medical Center, Dept of Radiation Oncology
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Carien Creutzberg, Chief Investigator, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT03469674    
Other Study ID Numbers: P16.054
UL2011-5336 ( Other Grant/Funding Number: Dutch Cancer Society )
ISRCTN11659025 ( Registry Identifier: ISRCTN Registry )
NTR5841 ( Registry Identifier: Netherlands Trials Registry )
First Posted: March 19, 2018    Key Record Dates
Last Update Posted: August 18, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Specifics will be decided and made public on website at a later stage, most probably from 5 years after final publication onwards
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: From 5 years after final publication onwards
Access Criteria: Upon written application with a clear decription of aim, methods and analysis plan, publication plan, after approval from the study team

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Carien Creutzberg, Leiden University Medical Center:
Radiotherapy
Vaginal brachytherapy
Molecular risk factors
Additional relevant MeSH terms:
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Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
 Uterine Diseases
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Diseases